Clofarabine, Cytarabine, and Idarubicin in Treating Patients With Intermediate-Risk or High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplasia

NCT ID: NCT00838240

Last Updated: 2012-07-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as clofarabine, cytarabine, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works when given together with cytarabine and idarubicin in treating patients with intermediate-risk or high-risk acute myeloid leukemia or high-risk myelodysplasia.

Detailed Description

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OBJECTIVES:

Primary

* To determine the optimum dose of clofarabine in combination with cytarabine and idarubicin in patients with previously untreated intermediate- and high-risk acute myeloid leukemia or high-risk myelodysplasia. (Phase I)
* To determine the safety and tolerance of this regimen in order to determine the recommended phase II dose. (Phase I)
* To explore the antitumor activity of this regimen in these patients. (Phase II)
* To determine the activity expressed as complete remission (CR)/CR with incomplete hematopoietic recovery (CRi) rate following induction therapy. (Phase II)

Secondary

* To determine the activity expressed as CR/CRi rate following induction (1 or 2 courses) and consolidation therapy. (Phase I)
* To determine hematopoietic recovery (platelets and neutrophils) after induction and consolidation therapy.
* To determine safety and tolerability of this regimen. (Phase II)
* To determine activity expressed as CR/CRi rate after consolidation therapy. (Phase II)
* To determine feasibility of blood CD34 harvesting after consolidation therapy. (Phase II)
* To determine disease-free and overall survival from CR/CRi. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of clofarabine followed by an randomized phase II study. Patients are stratified according to center, and presence of poor prognostic features (WBC at diagnosis ≥ 100,000/μL vs presence of very high risk cytogenetic features -5/5q-, -7/7q-, presence of complex abnormalities \[\> 3 abnormalities\], 3q, t\[6;9\], or t\[9;22\]). Patients are randomized to 1 of 2 treatment arms.

* Induction therapy:

* Arm I: Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.
* Arm II: Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.
* Consolidation therapy: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-6 and idarubicin IV over 5 minutes once daily on days 4-6.

After completion of study therapy, patients are followed periodically for 12 months.

Conditions

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Leukemia Myelodysplastic Syndromes

Keywords

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adult acute minimally differentiated myeloid leukemia (M0) adult acute myeloblastic leukemia without maturation (M1) adult acute myeloblastic leukemia with maturation (M2) adult acute myelomonocytic leukemia (M4) adult acute monoblastic leukemia (M5a) adult acute monocytic leukemia (M5b) adult erythroleukemia (M6a) adult pure erythroid leukemia (M6b) adult acute megakaryoblastic leukemia (M7) adult acute myeloid leukemia with 11q23 (MLL) abnormalities adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with t(8;21)(q22;q22) adult acute myeloid leukemia with inv(16)(p13;q22) untreated adult acute myeloid leukemia de novo myelodysplastic syndromes secondary acute myeloid leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I

Patients receive idarubicin IV over 5 minutes on days 1, 3, and 5, cytarabine IV continuously on days 1-10, and clofarabine IV over 1 hour on days 2, 4, 6, 8, and 10.

Group Type EXPERIMENTAL

clofarabine

Intervention Type DRUG

Given IV

cytarabine

Intervention Type DRUG

Given IV

idarubicin

Intervention Type DRUG

Given IV

Arm II

Patients receive idarubicin IV and cytarabine IV as in arm I. Patients also receive clofarabine IV by push injection over 10 minutes on days 2, 4, 6, 8, and 10.

Group Type EXPERIMENTAL

clofarabine

Intervention Type DRUG

Given IV

cytarabine

Intervention Type DRUG

Given IV

idarubicin

Intervention Type DRUG

Given IV

Interventions

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clofarabine

Given IV

Intervention Type DRUG

cytarabine

Given IV

Intervention Type DRUG

idarubicin

Given IV

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following by WHO criteria:

* Acute myeloid leukemia (AML) (≥ 20% bone marrow blasts by bone marrow aspiration or biopsy)

* No acute promyelocytic leukemia (M3)
* All cytogenetic groups allowed, except for the following:

* t(15;17)
* t(8;21) or inv(16) AND a WBC count at diagnosis of \< 100,000/μL
* Primary or secondary AML allowed, including AML after myelodysplasia (MDS)
* High-risk MDS (≥ 10% bone marrow blasts by bone marrow aspiration or biopsy)
* No chronic myelogenous leukemia in blast crisis or AML supervening a myeloproliferative disorder
* Previously untreated disease, except for ≤ 14 days of hydroxyurea
* No CNS leukemia

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* Serum creatinine ≤ 1.0 mg/dL or glomerular filtration rate \> 60 mL/min
* AST/ALT ≤ 2.5 times upper limit of normal (ULN)
* ALP ≤ 2.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier contraception during and for ≥ 3 months after completion of study treatment
* No active uncontrolled infection
* No HIV positivity
* No psychological, familial, sociological, or geographical conditions precluding compliance with study treatment or follow up
* No concurrent severe uncontrolled cardiovascular disease (i.e., symptomatic congestive heart failure or symptomatic ischemic heart disease \[NYHA class III-IV\])
* No concurrent malignant disease

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No concurrent cytotoxic drugs or experimental therapies (e.g., antiangiogenic drugs, tyrosine kinase inhibitors)
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roel Willemze

Role: PRINCIPAL_INVESTIGATOR

EORTC (Phase I) - Leiden University Medical Center, NL

Dominik Selleslag

Role: PRINCIPAL_INVESTIGATOR

EORTC (Phase II) - AZ Sint-Jan, BE

Giovanna Meloni

Role: PRINCIPAL_INVESTIGATOR

GIMEMA (Phase I & II) - Universita Degli Studi "La Sapienza", IT

Locations

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A.Z. Sint-Jan

Bruges, , Belgium

Site Status RECRUITING

Institut Jules Bordet

Brussels, , Belgium

Site Status NOT_YET_RECRUITING

CHU Sart-Tilman

Liège, , Belgium

Site Status NOT_YET_RECRUITING

University Hospital Rebro

Zagreb, , Croatia

Site Status NOT_YET_RECRUITING

Hôpital Saint Antoine AP-HP

Paris, , France

Site Status NOT_YET_RECRUITING

Azienda Ospedallera Universitaria - Policlinico Tor Vergata

Roma, , Italy

Site Status RECRUITING

Univesita Degli Studi "La Sapienza"

Roma, , Italy

Site Status RECRUITING

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Site Status RECRUITING

Leiden University Medical Center

Leiden, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Radboud University Nijmegen Medical Center

Nijmegen, , Netherlands

Site Status RECRUITING

Countries

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Belgium Croatia France Italy Netherlands

Central Contacts

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Hilde Breyssens

Role: CONTACT

Email: [email protected]

Other Identifiers

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EORTC-06061

Identifier Type: -

Identifier Source: secondary_id

EU-20905

Identifier Type: -

Identifier Source: secondary_id

2006-004912-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GIMEMA-AML-14A

Identifier Type: -

Identifier Source: secondary_id

EORTC-06061

Identifier Type: -

Identifier Source: org_study_id